Significant Publications

This work utilizes regional data from the greater Cincinnati area to demonstrate the importance of referral of “high risk” mothers to tertiary obstetrical centers for the care and delivery of their preterm infants. Maternal, rather than infant transfer, reduces perinatal morbidity and mortality related to preterm birth. This publication highlights the benefits of our regionalized clinical program.

This is a landmark publication, demonstrating the first effective treatment for the life-threatening pulmonary complications of lymphangioleiomyomatosis (LAM). It is a carefully controlled, double blind, multicenter study, led by Dr. McCormack (UC) and Dr. Trapnell (CCHMC-UC), began as a part of the “Rare Lung Disease Consortium” here at CCHMC.

It is increasingly clear that late preterm delivery poses significant risks to the newborn. This work demonstrates increased pulmonary morbidity, admission to special care units for multiple complications of prematurity, in spite of documented pulmonary maturation, a finding of national significance in reducing the rate of preterm birth and associated complications that occur even in late “preterms.” This work demonstrates that pulmonary maturity is not sufficient to ensure neonatal outcomes comparable to infants born at term.

Cooperation among Ohio delivery hospitals and the use of centralized databases, provide the infrastructure to document and reduce late onset sepsis in very preterm infants. This work demonstrates the value of a multi-center improvement collaborative to improve neonatal outcomes and reduce health care costs.

This work identifies secretor and nonsecretor status of the mother/infant dyad as an important risk factor for the necrotizing enterocolitis (NEC) and death of low birth weight/preterm infants. It is the first genetic test that indicates the risk for severe outcomes for preterm infants, and provides support for the importance of the innate immune system and its likely interaction with the microbiome in the pathogenesis of NEC and neonatal sepsis.

Division Highlights

Beena Kamath, MD, MPH

Dr. Kamath, along with colleagues Emily DeFranco, DO, (Dept. of OB/GYN University of Cincinnati) and Michael Marcotte, MD (Dept. of OB/GYN Good Samaritan Hospital), reported important findings regarding previously unappreciated limitations of fetal lung maturity testing to predict readiness for postnatal life.

These investigators led a pre-clinical study of MRI imaging using a novel prototype MRI developed by Dr. Chuck Dumoulin and his colleagues in the CCHMC Imaging Research Center. Preterm lambs were delivered by Cesarean section, treated with pulmonary surfactant, stabilized on mechanical ventilation and subjected to sequential MRI imaging. Successful studies of brain, lung, and gastrointestinal structures were conducted. Findings are being applied toward development of a clinical MRI device scheduled for installation in the CCHMC NICU by January 2012.

This group is working with the Anderson Center to support the CCHMC Community Health Strategic goal to reduce infant mortality in Hamilton County to the national average of 6.9/1000 live birth by 2015. They continue work on geographic analytic method to identify key “hot spots” for targeted interventions to reduce preterm birth through coordination of care.

Significant Accomplishments

Diagnosis and Treatment of Pulmonary Alveolar Proteinosis

National Institutes of Health funding was approved for Bruce Trapnell, MD, MS, and coworkers who have developed lung markers for the diagnosis of hereditary and acquired disorders of surfactant metabolism. They have found that pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder caused, in part, by autoimmunity against GM-CSF and by mutations in GM-CSF receptors, enabling correct diagnosis and treatment of these life-threatening disorders. New treatment modalities, including gene therapy, are being tested in the clinics.

Pathogenesis of Interstitial Lung Disease and Emphysema

New NIH funding was approved for studies, led by Timothy Weaver, PhD, to identify the mechanisms causing lung remodeling in idiopathic pulmonary fibrosis associated with mutations in the surfactant protein-C gene, a cause of life-threatening pulmonary disease in children and adults. Anne Karina Perl, PhD, leads the work identifying the role of growth factors to enhance lung growth in children and adults with emphysema.

Genetic Networks Linking Mucus Metaplasia and Inflammation

NIH funding was approved for the study of a new genetic network regulating airway epithelial cell differentiation and mucus production related to cystic fibrosis, asthma and COPD in work led by Thomas Korfhagen, MD, PhD, and Jeffrey Whitsett, MD. A master regulator of mucus production and its impact on lung structure and inflammation are being studied as a target for therapy for chronic lung diseases in children and adults.